Pharmaceutical Incompatibility

Introduction:
Incompatibility refers to the inability of something or some process to co-exist with another process or thing.
So, Pharmaceutical incompatibility refers to the inability of a pharmaceutical substance to exist in combination with another pharmaceutical entity.

Types of Incompatibility:

There are three types of incompatibility:

1. Therapeutical incompatibility

2. Chemical incompatibility

3. Pharmaceutical or physical incompability

1. Therapeutical incompatibility:

This incompabitlity is resulted due to the combination of drugs having antagonistic or opposing properties.

2. Chemical incompatibility:
This type of incompatibility is resulted due to the formation of undesirable new product when two or more drugs are combined.

Examples of Chemical incompatibility:
1. Precipitation
2. Colour change
3. Effervescences
4. Decomposition

Types of Chemical Incompatibility:
Chemical incompatibility can be intentional i.e. a prescriber knowingly gives incompatible drugs, or unintentional i.e. prescriber does not know that the drugs are incompatible.

There are two types of chemical incompatibility:

1. Tolerated
In this type of incompatibility, chemical reaction can be reduced by mixing the solution in dilute forms or by changing the order of mixing.

2. Adjusted
In this type of incompatibility, change in the formulation is needed with a compound of equal therapeutic value e.g. in the mixture of caffeine citrate and sodium salicylate, caffeine citrate is replaced with caffeine.

3. Pharmaceutical or physical Incompatibility:
This type of incompatibility results by the slow or immediate formation of decomposed solutions or precipitates, when the drugs are combined in a pharmacy setup or laboratoy.

Examples of Pharmaceutical or physical incompatibility:
1. Insolubility
2. Liquefaction
When the substances with low melting points such as camphor, menthol and thymol  are mixed together, a liquid mixture i.e. eutectic mixture is formed and this process is known as liquefaction.

3. Precipitation
Precipitation can result when the solvent in which the solute is insoluble is added to the solution. Resins are normally not soluble in water. So, the tinctures of resins may form precipitate on addition to water.

4. Immiscibility

Correction of pharmaceutical or physical incompatibiliy:

This can be corrected by using one or more of the following methods:

1. Addition of suspending agents or thickening agents:
In the following prescription tragacanth (mucilage or compound powder) is used as a suspending agent.

Phenacetin 3g
Caffeine 1g
Orange Syrup 12ml
Water upto 90ml

As Phenacetin is an indiffusible substance.

On the other hand, tinctures of resins are made soluble in water by the addition of some thickening agents or with vigorous stirring and shaking.

2. Emulsification:
Water and oil are immiscible in each other and they can be made miscible by the addition of Emulsions. This is known as Emulsification.

3. Changing the mixing or order of prescription

4. Changing the form of ingredients i.e. from liquid to solid form or from hydrous form to anhydrous form:
This is often helpful in increasing the solubility of a substance e.g.a solution of ephedrine sulfate, an alkaloidal salt, and liquid paraffin is not possible as alkaloidal salt of ephedrine sulfate is not soluble in liquid paraffin but anhydrous form of ephedrine is soluble in it. So we use anhydrous form.

Examples of Incompatibility:
1. Acids are incompatible with alkaline salts, carbonates and oxides. They causes the precipitation of albumin. So, acids are prescribed alone.

2. Bases and alkaline carbonates must not be prescribed alongwith other drugs in solution. They may precipitate metallic and alkaloidal salts.

Bibliography:
A text-book of materia medica and pharmacy for medical students

**REPRINT** Introduction to materia medica and pharmacology, including the elements of medical pharmacy, prescription writing, medical Latin, toxicology, and methods of local treatment


Survey of active pharmaceutical ingredients-excipient incompatibility: Nature and mechanism

Incompatibilities in prescriptions: For students in pharmacy and medicine and practicing pharmacists and physicians

Prescription writing: Including weights and measures, preparation of solutions, doses, administration and incompatibilities

Davis's Drug Guide for Nurses